BACKGROUNDMore than half of recurrent pregnancy loss (RPL) remains unexplained. We hypothesized that women with a history of unexplained RPL (URPL) have low venous reserve.METHODSCase-control study in 12 women with a history of URPL, 11 healthy nulliparous controls and 12 primiparous controls with a history of uncomplicated pregnancy. To quantify venous reserve, we measured plasma volume (PV, ml/m(2)) and venous compliance in forearm and calf (VC(arm), VC(calf), (ml/dl)/mmHg) during the follicular phase of the menstrual cycle. Mean arterial blood pressure (mmHg) was measured by oscillometry. Arterial demand was evaluated by cardiac index (CI, (l/min)/m(2)).RESULTSBaseline characteristics were comparable between groups. All groups had similar CI. Women with a history of RPL had 14% and 9% lower mean PV compared with nulliparous and primiparous controls (P < 0.01 and P = 0.04, respectively). In women with URPL, the mean VC(arm) was 25% and 32% lower compared with nulliparous and primiparous controls (P = 0.04 and P < 0.01, respectively), while the mean VC(calf) was 29 and 22% lower compared with the two control groups (P < 0.01 and P = 0.03, respectively).CONCLUSIONSWomen with URPL have lower venous reserves when compared with controls at comparable arterial demand. Interventions that increase venous reserve may improve pregnancy outcome.